This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. DNA. Though the details of catalysis by DNA cytosine-5 methyltransferases are currently known in great detail, the conformational changes that happen before the chemistry takes place have not yet been described. The mechanism by which DNA cytosine-5 methyltransferases target a particular cytosine for extrusion and later methylation is unknown. Hence our goal is to obtain structures of early intermediates of M.HaeIII bound to DNA before the catalysis occurs.